Citation and License

BMC Infectious Diseases 2010, 10:71
doi:10.1186/1471-2334-10-71

Published: 17 March 2010

Abstract

Background

Seasonal influenza imposes a substantial personal morbidity and societal cost burden.
Vaccination is the major strategy for influenza prevention; however, because antigenically
drifted influenza A and B viruses circulate annually, influenza vaccines must be updated
to provide protection against the predicted prevalent strains for the next influenza
season. The aim of this study was to assess the efficacy, safety, reactogenicity,
and immunogenicity of a trivalent inactivated split virion influenza vaccine (TIV)
in healthy adults over two influenza seasons in the US.

Methods

The primary endpoint of this double-blind, randomized study was the average efficacy
of TIV versus placebo for the prevention of vaccine-matched, culture-confirmed influenza
(VMCCI) across the 2005-2006 and 2006-2007 influenza seasons. Secondary endpoints
included the prevention of laboratory-confirmed (defined by culture and/or serology)
influenza, as well as safety, reactogenicity, immunogenicity, and consistency between
three consecutive vaccine lots. Participants were assessed actively during both influenza
seasons, and nasopharyngeal swabs were collected for viral culture from individuals
with influenza-like illness. Blood specimens were obtained for serology one month
after vaccination and at the end of each influenza season's surveillance period.

Results

Although the point estimate for efficacy in the prevention of all laboratory-confirmed
influenza was 63.2% (97.5% confidence interval [CI] lower bound of 48.2%), the point
estimate for the primary endpoint, efficacy of TIV against VMCCI across both influenza
seasons, was 46.3% with a 97.5% CI lower bound of 9.8%. This did not satisfy the pre-specified
success criterion of a one-sided 97.5% CI lower bound of >35% for vaccine efficacy.
The VMCCI attack rates were very low overall at 0.6% and 1.2% in the TIV and placebo
groups, respectively. Apart from a mismatch for influenza B virus lineage in 2005-2006,
there was a good match between TIV and the circulating strains. TIV was highly immunogenic,
and immune responses were consistent between three different TIV lots. The most common
reactogenicity events and spontaneous adverse events were associated with the injection
site, and were mild in severity.

Conclusions

Despite a good immune response, and an average efficacy over two influenza seasons
against laboratory-confirmed influenza of 63.2%, the pre-specified target (lower one-sided
97.5% confidence bound for efficacy > 35%) for the primary efficacy endpoint, the
prevention of VMCCI, was not met. However, the results should be interpreted with
caution in view of the very low attack rates we observed at the study sites in the
2005-2006 and 2006-2007, which corresponded to relatively mild influenza seasons in
the US. Overall, the results showed that TIV has an acceptable safety profile and
offered clinical benefit that exceeded risk.